The National Institute on Aging (NIA) Intramural Research Program (IRP) has been long interested in the cellular and molecular mechanisms of normative aging and age-related disease development. The program has pursued basic laboratory and longitudinal clinical research in normative aging to address these interests. NIA intramural investigators have expanded the program's capacity to address hypotheses about aging and health disparities in minority and poor populations. By posing fundamental questions about differences in rates and risks for pathological conditions associated with aging, studying groups with diverse racial, ethnic, and economic origins, IRP clinical researchers hope to understand the significance of environmental and genetic risk factors for disease. The need to understand the driving factors behind persistent black-white health disparities in overall longevity, cardiovascular disease, and cerebrovascular disease, has led to the effort to develop and plan the NIA IRP Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study is a community-based, epidemiologically driven research effort designed to focus on evaluating health disparities in socioeconomically diverse African Americans and whites in Baltimore. This study is unique because it is a multidisciplinary project that assesses physical parameters as well as evaluating genetic, biologic, demographic, psychosocial, and psychophysiological parameters of Black and White participants in higher and lower socioeconomic status (SES) over a 20-year period. It also employs novel research tools, mobile medical research vehicles to improve participation rates and retention among non-traditional research participants. The initial examination and recruitment phase will take approximately 3 years to complete. The study data will be collected in two parts. The first part consists of an in-home interview that includes questionnaires about the participant's health status, health service utilization, psychosocial factors, nutrition, neighborhood characteristics, and demographics. The second part will be collected on the medical research vehicles and includes medical history and physical examination, dietary recall, cognitive evaluation, psychophysiology assessments including heart rate variability, arterial thickness, carotid ultrasonography, assessments of muscle strength and bone density, and laboratory measurements (blood chemistries, hematology, biomarkers of oxidative stress and biomaterials for genetic studies The HANDLS study is a multidisciplinary, prospective epidemiologic longitudinal study examining the influences and interaction of race and SES on the development of cardiovascular and cerebrovascular health disparities among minority and lower SES subgroups. The baseline HANDLS sample will consist of approximately 4,000 community-dwelling African American and white adults aged 30-64. Participants are being drawn from 12 pre-determined census tracts in Baltimore City, sampling representatively across a wide range of socioeconomic and income circumstances. The heuristic study design is a factorial cross of four factors: age, sex, race, and SES with approximately equal numbers of subjects per "cell." HANDLS is planned as a 20-year longitudinal study. Using our mobile medical research vehicles, we will visit each census tract for 3 months and we will re-visit every census tract in a 3-year cycle. The 12 census tracts identified were selected because they are likely to yield representative distributions of individuals between 30 and 64 years old who are African Americans and whites, men and women, and lower and higher SES. Individuals calling themselves multi-ethnics will be included and categorized by the group with which they most strongly identify, but their multi-ethnic identification will be recorded for subsequent statistical analyses. Multi-ethnic individuals who identify strongly with neither African Americans nor whites will be excluded from the present study. Initial estimates based on the 2000 census data indicate that we will need to visit approximately 35% of the households in each census tract to collect the required 333 individuals. The initial sample of 4,000 participants is based on power analyses and assumptions about attrition over 20 years. For a power of 80% (the likelihood of finding an effect if it is really present), we can identify moderate effects (magnitude of the differences between groups) for various outcomes with as few as 30 participants per group at the end of the study. Working backwards by assuming 20% attrition after the baseline assessment and 15% attrition between subsequent assessments, we need approximately 4,000 participants at baseline to yield 1,680 after 20 years. The recruitment phase and initial examination will take approximately 3 years to complete. The study has completed a pilot phase that was conducted in two waves (October 2000-December 2001 and February 2003-November 2003). The epidemiologic phase of the study began in August 2004 with a field based dress rehearsal, currently in progress. The full study will begin on November 1, 2004 in the Reservoir Hill area of Baltimore. Covariates-- Other variables such as nutrition, environment and neighborhood effects, genetic make-up, family history, activity level, access to health care, and prevalent medical, dental, psychiatric conditions, oxidative stress, and DNA repair capacity may modulate the effects of SES and race on cardiovascular, musculoskeletal, cognitive, and autonomic functioning. For example: The nutritional domain of the study will examine the effects of race socioeconomic status (SES) on nutritional status and identify nutritional factors that may contribute to health disparity in cardiovascular and cerebrovascular health and cognitive function. The biomarkers domain of the study will examine possible biologic covariates of health disparities and aging. The early appearance and increased severity of age-associated disease among African Americans and low SES individuals suggests that the factors contributing to the emergence of health disparities may also induce a phenotype of 'premature aging' or "accelerated agin". While we do not posit that health disparities result from genetic alterations in genes associated with the known heritable progeroid syndromes. We do hypothesize that in low SES populations with high rates of early onset age-associated disease the interaction of biologic, psychosocial, socioeconomic and environmental factors may result in a phenotype of accelerated aging biologically similar to these syndromes with increased susceptibility to oxidative stress, premature accumulation of oxidative DNA damage, defects in DNA repair and higher levels of biomarkers of oxidative stress. Health disparities therefore, may be the end product of this complex interaction in populations at high risk. HANDLS will examine this hypothesis by measuring biomarkers of oxidative stress, assessing levels of the most widely studied oxidative DNA adduct, and measuring DNA repair capacity in study participants. Prospectively measuring biomarkers of oxidative stress in a longitudinal study may clarify whether oxidative stress plays a pivotal role in aging and in the development and or progression of age associated disease. It may also provide insights into the different trajectories of aging observed in individuals.